The effects of Bone Morphogenetic Protein 4 on adult neural stem cell proliferation, differentiation and survival in an in vitro model of ischemic stroke.

The subventricular zone (SVZ) of the lateral ventricles represents a main region where neural stem cells (NSCs) of the mature central nervous system (CNS) reside. Bone Morphogenetic Proteins (BMPs) are the largest subclass of the transforming growth factor-β (TGF-β) superfamily of ligands. BMP4 is one such member and plays important roles in adult NSC differentiation. However, the exact effects of BMP4 on SVZ adult NSCs in CNS ischemia are still unknown. Using oxygen and glucose deprivation (OGD) as an in vitro model of ischemia, we examined the behavior of adult NSCs. We observed that anoxia resulted in reduced viability of adult NSCs, and that BMP4 treatment clearly rescued apoptotic cell death following anoxia. Furthermore, BMP4 treatment exhibited a strong inhibitory effect on cellular proliferation of the adult NSCs in normoxic conditions. Moreover, such inhibitory effects of BMP4 treatment were also found in OGD conditions, despite the enhanced cellular proliferation of the adult NSCs that was observed under such ischemic conditions. Increased neuronal and astroglial commitment of adult NSCs were found in the OGD conditions, whereas a reduction in differentiated neurons and an increase in differentiated astrocytes were observed following BMP4 treatment. The present data indicate that BMP4 modulates proliferation and differentiation of SVZ-derived adult NSCs and promotes cell survival in the in vitro model of ischemic stroke.